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Published on: January 7, 2019
Apelin-13 regulates LPS-induced N9 microglia polarization involving STAT3 signaling pathway
Shouhong Zhou1, Xiaoxiao Guo1, Shanshan Chen1
1Department of Physiology, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China.
Abstract:
The process of neurodegenerative diseases has always been accompanied by neuroinflammatory response characterized by microglia activation. Two phenotypes of microglial polarization: the classically activated M1 type and the alternative activated M2 type, have been described. Although apelin-13 has been shown to have neuroprotective effects, its specific mechanism of anti-neuritis is still unclear. The aim of this study was to investigate whether apelin-13 can exert anti-neuroinflammatory effects by regulating the polarization of N9 microglia. MTT assay showed that 0.1 μM apelin-13 (24 h) and 2 μg/mL LPS (6 h) treatment had no significant effect on cell viability of N9 microglia. The combined treatment of Apelin-13 and LPS did not affect the viability of N9 microglia. N9 microglia were pretreated with 0.1 μM apelin-13 for 24 h, followed by incubation with LPS for 6 h. Morphological results indicated that apelin-13 (0.1 μM) inhibited LPS-induced N9 microglial activation as observed by smaller soma and slender process compared to LPS-treated group. Western blot confirmed that apelin-13 decreased the level of proinflammatory factor iNOS, IL-6 and up-regulated the level of anti-inflammatory factor arg-1 and IL-10 in N9 microglia. Flow cytometry revealed that apelin-13 inhibited the expression of M1 microglia activation marker CD86 and up-regulated the expression of M2 marker CD206. Furthermore, the data displayed that apelin-13 decreased the expression of p-STAT3 and the radio of p-STAT3/t-STAT3 in M1-type N9 microglia induced by LPS. In conclusion, our results indicated apelin-13 ameliorated neuroinflammation by shifting N9 microglial M1 polarization toward the M2 phenotype, the underlying mechanism of which may be related to STAT3 signals.
Insights
Apelin-13 peptide reduces neuroinflammation by shifting microglia from M1 to M2 phenotypes. This mechanism involves regulating STAT3 signaling, offering potential therapeutic benefits for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Neurodegenerative diseases involve neuroinflammation driven by microglia activation.
- Microglia exhibit M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes.
- Apelin-13's neuroprotective effects are known, but its anti-neuroinflammatory mechanism is unclear.
Purpose of the Study:
- To investigate if apelin-13 reduces neuroinflammation by modulating N9 microglia polarization.
- To elucidate the specific molecular pathways involved in apelin-13's effects on microglia.
Main Methods:
- N9 microglia were treated with apelin-13 and lipopolysaccharide (LPS).
- Cell viability was assessed using MTT assay.
- Microglial morphology, inflammatory markers (iNOS, IL-6, arg-1, IL-10), polarization markers (CD86, CD206), and STAT3 signaling were analyzed via Western blot and flow cytometry.
Main Results:
- Apelin-13 (0.1 μM) did not affect N9 microglia viability.
- Apelin-13 inhibited LPS-induced M1 microglia activation and promoted M2 phenotype.
- Apelin-13 decreased pro-inflammatory factors (iNOS, IL-6) and increased anti-inflammatory factors (arg-1, IL-10).
- Apelin-13 reduced M1 marker CD86 and increased M2 marker CD206 expression.
- Apelin-13 suppressed p-STAT3 and the p-STAT3/t-STAT3 ratio in M1 microglia.
Conclusions:
- Apelin-13 ameliorates neuroinflammation by promoting M1 to M2 microglial polarization.
- The underlying mechanism may involve the regulation of STAT3 signaling pathways.
- Apelin-13 shows potential as a therapeutic agent for neuroinflammatory conditions.
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